Alterations in microRNA expression profiles in inflamed and noninflamed ascending colon mucosae of patients with active Crohn's disease

J Gastroenterol Hepatol. 2017 Oct;32(10):1706-1715. doi: 10.1111/jgh.13778.

Abstract

Background and aim: The microRNA (miRNA) expression profiles of the terminal ileum, sigmoid colon, and rectal mucosa of adult patients with active Crohn's disease (CD) have been previously reported. The purpose of this study was to identify dysregulated miRNAs in the mucosa of the ascending colon.

Methods: Biopsy tissue samples were taken from the mucosae of inflammatory (iCD) or noninflammatory (niCD) areas of the ascending colons of adult patients with active CD. miRNA and mRNA expression profiles were detected using microarray analyses. miRNAs and messenger RNAs (mRNAs) demonstrating significant differences were validated via quantitative real-time polymerase chain reaction. Luciferase reporter genes were used to measure two miRNAs inhibition of potential target genes in human 293T cells in vitro.

Results: Compared with the healthy control group, the ascending colon miRNA expression profiles revealed that 43 miRNAs were significantly upregulated and 35 were downregulated in the iCD group. The mRNA expression profiles indicated that 3370 transcripts were significantly differentially expressed in the ascending colon, with 2169 upregulated and 1201 downregulated mRNAs in the iCD group, and only 20 miRNAs demonstrated significant differential expression in the niCD group. In contrast, nearly 100 miRNAs significantly varied between the iCD and niCD groups. Finally, luciferase reporter gene assays showed that hsa-miR-16-1 directly regulated the human C10orf54 gene and that they were negatively correlated.

Conclusions: Our results indicated that the differentially expressed miRNAs and mRNAs were related to immune inflammation and intestinal flora. The data provide preliminary evidence that the occurrence of CD involves the inhibition of C10orf54 expression by hsa-miR-16-1.

Keywords: Crohn's disease; ascending colon mucosa; mRNAs; microRNA expression profiles.

MeSH terms

  • Colon, Ascending / metabolism*
  • Colon, Ascending / microbiology
  • Crohn Disease / genetics*
  • Crohn Disease / metabolism*
  • Gastrointestinal Microbiome
  • HEK293 Cells
  • Humans
  • Inflammation / genetics
  • Inflammation / metabolism
  • Intestinal Mucosa / metabolism*
  • Intestinal Mucosa / microbiology
  • MicroRNAs / genetics*
  • MicroRNAs / metabolism
  • RNA, Messenger / genetics
  • RNA, Messenger / metabolism
  • Transcriptome / genetics*
  • Tumor Suppressor Proteins

Substances

  • MIRN16 microRNA, human
  • MicroRNAs
  • RNA, Messenger
  • Tumor Suppressor Proteins
  • long non-coding RNA CASC2, human